scholarly journals Enzyme–Inhibitor Interactions and a Simple, Rapid Method for Determining Inhibition Modality

2019 ◽  
Vol 24 (5) ◽  
pp. 515-522 ◽  
Author(s):  
Shane M. Buker ◽  
P. Ann Boriack-Sjodin ◽  
Robert A. Copeland
Keyword(s):  
Drug Discovery ◽  
Substrate Concentration ◽  
Chemical Biology ◽  
Enzyme Inhibitor ◽  
Specific Inhibition ◽  
Experimental Conditions ◽  
The Common ◽  
Inhibitory Molecules ◽  
The Impact

Contemporary chemical biology and drug discovery are increasingly focused on the discovery of inhibitory molecules that interact with enzyme targets in specific ways, such as allosteric or orthosteric binding. Hence, there is increasing interest in evaluating hit compounds from high-throughput diversity screening to determine their mode of interaction with the target. In this work, the common inhibition modalities are reviewed and clarified. The impact of substrate concentration, relative to substrate KM, for each common inhibition modality is also reviewed. The pattern of changes in IC50 that accompany increasing substrate concentration are shown to be diagnostic of specific inhibition modalities. Thus, replots of IC50 as a function of the ratio [S]/KM are recommended as a simple and rapid means of assessing inhibition modality. Finally, specific recommendations are offered for ideal experimental conditions for the determination of inhibition modality through the use of IC50 replots.

scholarly journals Assessment of Salivary Catalase, α-Amylase, and Cotinine Levels in Chronic Smokers: A Comparative Study

2018 ◽  
Vol 19 (3) ◽  
pp. 253-256 ◽  
Author(s):  
Satvinder Singh ◽  
Mamta Sharma ◽  
Nitika Rohilla ◽  
Varun Salgotra ◽  
Varun Kumar ◽  
...  
Keyword(s):  
Comparative Study ◽  
Harmful Effect ◽  
Study Groups ◽  
Potential Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Salivary Cotinine ◽  
Elisa Technique ◽  
The Common ◽  
The Impact

ABSTRACT Introduction One of the common practices observed in many parts of the world is smoking, of which tobacco forms an important constituent which is burned and inhaled. Smoking is known to have potential effect on body’s immune system, antioxidants level, and salivary cotinine levels. Hence, we planned the present study to evaluate the impact of cigarette smoke on salivary antioxidant levels and cotinine levels in smokers and nonsmokers. Materials and methods The present study included assessment of salivary parameters of smokers and nonsmokers. A total of 400 subjects were analyzed, of which 200 were active smokers and 200 were nonsmokers. Unstimulated salivary samples were taken and assessment of α-amylase levels was done using biochemical kit and spectrophotometer. Assessment of salivary catalase (CAT) activity was done using Luck method. For the determination of cotinine levels, Bioassay Technology Laboratory kit was used using enzyme-linked immunosorbent assay (ELISA) technique. After the assessment of levels of all the salivary parameters, all the data were recorded, compiled, and analyzed. Results α-Amylase in smokers and nonsmokers group was found to be 206.25 and 169.85 U/mL respectively. Nonsignificant results were obtained while comparing the salivary α-amylase levels among the two study groups. Nonsignificant results were obtained while comparing the salivary CAT levels among the smokers and nonsmokers group. We observed statistically significant results while comparing mean cotinine levels among smokers group and nonsmokers group. Conclusion Alteration in cotinine levels occurs in smokers in comparison to nonsmokers. Clinical significance Smoking can cause harmful effect on the oral mucous membrane by altering salivary defense components. How to cite this article Singh S, Sharma M, Rohilla N, Salgotra V, Kumar V, Sharma RK. Assessment of Salivary Catalase, α-Amylase, and Cotinine Levels in Chronic Smokers: A Comparative Study. J Contemp Dent Pract 2018;19(3):253-256.

scholarly journals The effects of subchronic exposure to ketoprofen on early developmental stages of common carp

2013 ◽  
Vol 82 (3) ◽  
pp. 343-347 ◽  
Author(s):  
Eva Prášková ◽  
Stanislava Štěpánová ◽  
Lucie Chromcová ◽  
Lucie Plhalová ◽  
Eva Voslářová ◽  
...  
Keyword(s):  
Common Carp ◽  
Surface Waters ◽  
Developmental Stages ◽  
Experimental Conditions ◽  
Environmental Concentration ◽  
Negative Effect ◽  
Rate Evaluation ◽  
The Impact ◽  
Early Developmental

Ketoprofen residues have been found in surface water where they present a potential risk to nontarget aquatic species. The aim of this study was to assess the impact of ketoprofen in surface waters on fish under experimental conditions. Subchronic toxic effects on 300 embryos and larvae of common carp (Cyprinus carpio) were investigated during a 30 day toxicity test with concentrations of ketoprofen: 0.003, 2.1, 6.3 and 21 mg/l. The exposure to ketoprofen showed no effect on mortality, but we observed significant delay (P < 0.05) in hatching in day 3 in fish exposed to all concentrations of ketoprofen. Significant delays (P < 0.05) in development were revealed at 2.1, 6.3 and 21 mg/l ketoprofen. On the basis of weight and growth rate evaluation and the determination of developmental stages, the lowest observed effect concentration was 0.003 mg/l. According to these results, the reported environmental concentration of ketoprofen in Czech rivers could have a negative effect on the growth and development of carp embryos and larvae. These tests have not yet been performed. Further research and search for a mechanism to reduce the incidence of ketoprofen in the waters by better wastewater treatment is required.

scholarly journals Interpretation of ponded infiltration data using numerical experiments

2016 ◽  
Vol 64 (3) ◽  
pp. 289-299 ◽  
Author(s):  
Michal Dohnal ◽  
Tomas Vogel ◽  
Jaromir Dusek ◽  
Jana Votrubova ◽  
Miroslav Tesar
Keyword(s):  
Hydraulic Conductivity ◽  
Saturated Hydraulic Conductivity ◽  
Experimental Conditions ◽  
Insertion Depth ◽  
Retention Capacity ◽  
Soil Layering ◽  
Soil Hydraulic ◽  
The Impact ◽  
Infiltration Experiment

AbstractPonded infiltration experiment is a simple test used for in-situ determination of soil hydraulic properties, particularly saturated hydraulic conductivity and sorptivity. It is known that infiltration process in natural soils is strongly affected by presence of macropores, soil layering, initial and experimental conditions etc. As a result, infiltration record encompasses a complex of mutually compensating effects that are difficult to separate from each other. Determination of sorptivity and saturated hydraulic conductivity from such infiltration data is complicated. In the present study we use numerical simulation to examine the impact of selected experimental conditions and soil profile properties on the ponded infiltration experiment results, specifically in terms of the hydraulic conductivity and sorptivity evaluation. The effect of following factors was considered: depth of ponding, ring insertion depth, initial soil water content, presence of preferential pathways, hydraulic conductivity anisotropy, soil layering, surface layer retention capacity and hydraulic conductivity, and presence of soil pipes or stones under the infiltration ring. Results were compared with a large database of infiltration curves measured at the experimental site Liz (Bohemian Forest, Czech Republic). Reasonably good agreement between simulated and observed infiltration curves was achieved by combining several of factors tested. Moreover, the ring insertion effect was recognized as one of the major causes of uncertainty in the determination of soil hydraulic parameters.

scholarly journals The Impact of Chemical Biology on Drug Discovery

2019 ◽  
Vol 59 (1-2) ◽  
pp. 29-36
Author(s):  
Oliver Plettenburg
Keyword(s):  
Drug Discovery ◽  
Chemical Biology ◽  
The Impact

Does Unconscious Information Affect Cognitive Activity?: A Study Using Experimental Priming

2011 ◽  
Vol 14 (1) ◽  
pp. 20-36 ◽  
Author(s):  
Margarita G. Filippova
Keyword(s):  
Information Processing ◽  
Priming Effect ◽  
Choice Model ◽  
Cognitive Activity ◽  
Processing System ◽  
Spreading Activation ◽  
Experimental Conditions ◽  
Priming Paradigm ◽  
The Impact

In a series of three experiments the influence that information unrecognised by the subjects has on the effectiveness of occurring cognitive activity is studied. With this aim 3 types of stimulus were compared which for one reason or another were not afforded sufficient attention, namely: unconscious meanings of polysemantic information, stimuli presented at the subliminal level, and intentionally ignored distractors. All the listed types of stimuli are united in that the subjects were not able to give an account of them, i.e., these stimuli were not processed attentively. It is assumed that each of the types of stimuli studied is in actuality perceived, which can be judged by the impact they have on occurring cognitive activity. The purpose of the present research is the comparison of this impact: apart from the determination of the impact of unperceived stimuli on the information directly associated with them (priming-effect registration), also identified is the presence/absence of an overall interference effect rendered by the unperceived stimuli on the performance of occurring cognitive activity. To this end, each experiment had a control condition the aim of which was the creation of the possibility for the subjects to perceive stimuli unnoticed under experimental conditions. An experimental priming paradigm was used in combination with image-classification and lexical-decision tasks.The results of the experiments conducted demonstrate that all types of stimuli ‘slipping the attention’ are assimilated, but their effect on occurring cognitive activity is varied. Thus, subliminally presented information aids, and distractors, on the contrary, hinder the solution of tasks associated with them, whereas unperceived meanings of polysemantic information hinder not only the solution of the tasks directly associated with them, but also the performance of any other cognitive activity for which they serve as a context. The effect of subliminal stimuli on occurring cognitive activity in the present research is explained by the spreading activation in the memory, the effect of distractors – by the inhibition of irrelevant representations in the information-processing system. For an explanation of the consequence of unperceived meanings of polysemanticity, not only an inhibition model was used, but also an unconscious negative choice model which assumed the necessity of making a special decision on non-perception.

High-Throughput Mechanism of Inhibition

2021 ◽  
Vol 26 (2) ◽  
pp. 248-256
Author(s):  
Gareth Davies ◽  
Hannah Semple ◽  
Megan McCandless ◽  
Jonathan Cairns ◽  
Geoffrey A. Holdgate
Keyword(s):  
High Throughput ◽  
Substrate Concentration ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Significant Proportion ◽  
Mechanism Of Inhibition ◽  
The Common ◽  
High Throughput Screens ◽  
The Impact ◽  
Druggable Genome

Enzymes represent a significant proportion of the druggable genome and constitute a rich source of drug targets. Delivery of a successful program for developing a modulator of enzyme activity requires an understanding of the enzyme’s mechanism and the mode of interaction of compounds. This allows an understanding of how physiological conditions in disease-relevant cells will affect inhibitor potency. As a result, there is increasing interest in evaluating hit compounds from high-throughput screens to determine their mode of interaction with the target. This work revisits the common inhibition modalities and illustrates the impact of substrate concentration relative to Km upon the pattern of changes in IC50 that are expected for increasing substrate concentration. It proposes a new, high-throughput approach for assessing mode of inhibition, incorporating analyses based on a minimal descriptive model, to deliver a workflow that allows rapid and earlier compound classification immediately after high-throughput screening.

Nomads of the Steppe Ciscaucasia during the Great Reforms in Russia

2021 ◽  
Vol 20 (1) ◽  
pp. 74-87
Author(s):  
Irina V. Lidzhieva ◽  
Daniyal S. Kidirniyazov
Keyword(s):  
Russian Revolution ◽  
Periodical Press ◽  
Vital Activity ◽  
Genetic Method ◽  
Archival Documents ◽  
The Common ◽  
The Russian Empire ◽  
Regional Authorities ◽  
The Impact

Based on an analysis of archival documents and periodical press materials, the present paper studies the impact of the liberal reforms of Alexander II on the policies of the imperial authorities for the nomadic peoples of the steppe of Ciscaucasia: the Kalmyks, Nogais and Turkmens. The liberal reforms of the 1860s and 1870s had a direct impact on the formation of the national intelligentsia, which during the revolutionary events of the early 20th century led to the rise of the national movement in the empires peripheries and to the struggle for self-determination of the non-Russian populations during the Russian Revolution of 1917. The article reconstructs individual facts and events from the life of the nomadic population under specific socio-economic and political-legal conditions. Using the historical-genetic method, the influence of liberal reforms on the vital activity of the nomadic peoples of the Stavropol province is revealed. The authors focus on the activities of regional authorities during the period under review, which were liberal in nature and carried out in the context of the reforms of Alexander II. The authors conclude that the pre-Caucasus steppe, the territory of the nomadic Kalmyks, Nogais and Turkmens, being the national edge of the Russian Empire and falling under a special system of governance related to the ethnic and religious characteristics of the populations, was not drawn into the orbit of liberal reforms. Meanwhile, a number of measures were approved by the regional executive authorities on the ground, of course, first of all, aimed at satisfying the needs of the imperial policy for incorporating the region into the common imperial space, but at the same time improving the lives of the nomadic peoples of the Stavropol province, in particular in the field of education and legal procedures.

scholarly journals Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes

2020 ◽  
Author(s):  
Zongtao Lin ◽  
Xie Wang ◽  
Katelyn A Bustin ◽  
Lin He ◽  
Radu M Suciu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Active Site ◽  
Chemical Biology ◽  
Tissue Imaging ◽  
Single Type ◽  
Functional Classes ◽  
The Common ◽  
Enzyme Cofactors ◽  
Transient Intermediates ◽  
Substituted Hydrazines

Known chemoproteomic probes generally use warheads that tag a single type of amino acid or modified form thereof to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electron-poor enzyme cofactors, transient intermediates and chemically-labile regulatory modifications, but probes for such species are underdeveloped. Here, we have innovated a versatile class of chemoproteomic probes for this less charted hemisphere of the proteome by using hydrazine as the common chemical warhead. Its electron-rich nature allows it to react by both polar and radicaloid mechanisms and to target multiple, pharmacologically important functional classes of enzymes bearing diverse organic and inorganic cofactors. Probe attachment can be blocked by active-site-directed inhibitors, and elaboration of the warhead supports connection of a target to a lead compound. The capacity of substituted hydrazines to profile, discover and inhibit diverse cofactor-dependent enzymes enables cell and tissue imaging and makes this platform useful for enzyme and drug discovery.

scholarly journals Approximations, Errors, and Misconceptions in the Use of Map Projections

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sergio Baselga ◽  
Michael J. Olsen
Keyword(s):  
Remote Sensing ◽  
Reference Systems ◽  
Geospatial Information ◽  
Map Projections ◽  
Scale Factors ◽  
Common Causes ◽  
The Common ◽  
The Impact ◽  
Area Determination

Global geodetic techniques currently can provide the user with worldwide millimeter accuracy. Preservation of this degree of accuracy in derived products is far from straightforward and may leave vast room for trouble in the different steps involved in the collection, storing, processing, analysis, and delivering of geospatial information. This paper is envisioned to serve as a guide for those utilizing map projections, in any possible form of application-cartography, GIS, remote sensing, photogrammetry, etc., to the common (and not so common) causes of error and misconception. This work also explores and questions the validity of some of approximations that are routinely implemented and quantifies the corresponding impact. These include the impact of neglecting meteorological corrections, reduction to ellipsoid and grid scale factors for distances, meridian convergence and arc-to-chord correction for angles, and mixing up with different frames and reference systems, height systems, or deceptively similar map projections. Correct indications are also given for accurately performing geospatial operations such as intersection of lines, determination of minimum point to line distance, and area determination for cadaster, which are often performed with suboptimal accuracy.

scholarly journals Development of a new procedure for the determination of the reactivity of brandies used in wine fortification

OENO One ◽  
2021 ◽  
Vol 55 (3) ◽  
pp. 161-172
Author(s):  
Joana Azevedo ◽  
João Pissarra ◽  
Filipa Amaro ◽  
Luis Guido ◽  
Joana Oliveira ◽  
...  
Keyword(s):  
Reaction Time ◽  
Coefficient Of Variation ◽  
Condensed Tannins ◽  
New Method ◽  
Reactivity Index ◽  
Visible Spectroscopy ◽  
Experimental Conditions ◽  
The Impact ◽  
Reproducibility Limit

The main purpose of this work was to describe and validate a new methodology for the determination of a brandy reactivity index (BRI) towards flavan-3-ol compounds in wines (catechins and condensed tannins) and to correlate this index with the amount and type of aldehydes present in those brandies. This new method consists of two main reactions: a) the ability of aldehydes to react with C8 and/or C6 positions in the phloroglucinol ring of a catechin present in excess (A ring); b) further reaction of the remaining free catechin with p-dimethylaminocinamaldehyde (DMACA) yielding to the formation of a blue compound that can be quantified by Visible spectroscopy at 640 nm. The impact of different experimental conditions such as reagent concentrations and reaction time on BRI were also evaluated. The method was validated through the determination of repeatability (intra-day variability) and reproducibility. The repeatability was considered acceptable with a CV of 11.87 %. The analysis of the reproducibility variance, S2R (11.59), the reproducibility limit R (9.5) and the reproducibility coefficient of variation, CVR (15.25 %) postulates BRI methodology to be reliable and robust.Using the developed methodology, the BRI of fourteen different commercial brandies and some pure standards aldehydes were determined. The aldehydes present in brandies, and the content of total aldehydes were determined by GC-MS and then correlated with the BRI. In general, it was observed a direct correlation between the BRI and the concentration of total aldehydes, in particular acetaldehyde.

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